In the field of Tissue Engineering, the research about engineering of skin substitutes represents an innovative and promising approach to heal acute and chronic skin wounds, reducing requirements for donor skin autograft The aim of this review is to illustrate the evolutive course of skin substitutes, putting in evidence the main steps happened thanks to the important mputs coming from biotechnologies progresses and clinical practice. The starting point of this evolutive course was the confirmed possibility to obtain in vitro epidermic equivalents (CEA) prepared from cultured skin cells and biopolymers. Since then the research in bioengineering skin, moved by clinical pressing of reconstructive and burn surgery made progresses trying to develop cutaneous substitutes very similar to native skin by a morpho-functional point of view. So it has been possible, starting from a 2 × 2 cm skin human biopsy, to realize completely autologous cutaneous substitutes not only composed of two main structures of skin, dermis and epidermis, but containing also other important components: microvascular network, micronervous network, skin immunocompetent system and melanocyte system The final goal is to develop effective and easy handling skin substitutes that could reproduce human skin anatomy and physiology introducing new advantages linked to successful grafting and then to satisfactory clinical results by functional and aesthetic point of view.
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